Runxl (AML1) encodes a DNA-binding subunit of the core-binding factors (CBFs). Runxl is required for the emergence of hematopoietic stem cells (HSCs) during embryogenesis, and is expressed in HSCs. Here we propose to examine Runxl expression and function in other stem cell populations in the adult mouse bone marrow and midgestation mouse fetus. Several laboratories have shown that cells isolated from the bone marrow can contribute to the formation of skeletal muscle, heart muscle and endothelial cells, and liver hepatocytes. We will determine whether Runxl expression marks stem cells in the bone marrow capable of contributing to these tissues, or conversely if Runxl expression can be used to separate muscle, heart, and liver stem cells from HSCs. We will also determine whether Runxl is required for the developmental emergence of stem cells for skeletal muscle, heart muscle and endothelial cells, and liver hepatocytes. Finally, we plan to identify target genes for Runxl that are expressed in newly emerging HSCs in the mouse embryo.